September 26, 1995
Media Contact: John Cramer
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Results of a new Johns Hopkins study show that chronic fatigue syndrome is strongly linked to a common and potentially treatable abnormality of blood pressure regulation.
The findings, reported in the Sept. 27 issue of The Journal of the American Medical Association, link CFS with a blood pressure regulation disorder called neurally mediated hypotension and advance earlier work that drew similar conclusions among fatigued adolescents. Both studies found that symptoms such as exhaustion, exercise intolerance, muddled thinking, and dizziness cleared after neurally mediated hypotension was diagnosed and treated.
"This study is the first to demonstrate that the symptoms of CFS can be improved with treatment directed at neurally mediated hypotension," says Hugh Calkins, M.D., associate professor of medicine and pediatrics and director of electrophysiology. "Further research will help us define the basis of the link and a randomized, placebo-controlled study is still needed to confirm the favorable response to therapy that we observed."
In the Hopkins study, 22 of 23 patients (18 women, five men, median age 34 years) with CFS tested positive for neurally mediated hypotension. After treatment, nine patients reported full recovery from fatigue and seven others noted some improvement, say researchers.
Neurally mediated hypotension cannot be detected during a routine blood pressure or heart rate screening. Tilt testing, available in most hospitals and academic centers throughout the United States, is the only means of positive diagnosis.
Each patient in the Hopkins study underwent all or part of a head-up, three-stage tilt table test. The tilt table rests at a 70-degree angle to simulate standing for long periods -- a common trigger of neurally mediated hypotension (NMH). Heart rate and blood pressure were monitored throughout the test.
Of the 22 patients diagnosed with NMH, all experienced lightheadedness, nausea or fainting and a 25 mmHg decrease in systolic blood pressure without an associated increase in heart rate. All became tired and lethargic and remained so for several days after the test, suggesting that fatigue can become chronic if neurally mediated hypotension occurs frequently enough, says Calkins.
Sixteen of the 22 CFS patients who tested positive did so at the first stage of the tilt test, unlike four of 14 controls (10 women, 4 men, median age 36 years) who tested positive, at a much later point after a drug was administered to simulate high adrenaline levels. "The difference is that those with CFS generally had a drop in blood pressure more quickly and without artificial stimulation," explains Peter Rowe, M.D., the pediatrician who first made the link between the two disorders.
Patients with neurally mediated hypotension were treated with drugs commonly used to regulate blood pressure. While some of the drugs work by allowing the kidneys to retain more sodium, others block the body's response to adrenaline, a kick-starter of the blood pressure abnormality.
More than half of the patients experienced some improvement over time, but the researchers say that compliance with these drug therapies proved challenging.
"It takes a great deal of persistence from the patient and physician to find the right combination for each individual," says Rowe. Careful monitoring by a physician is required because the drugs pose a risk of serious side effects such as excessive elevation in blood pressure or depression. In addition, patients often need to change therapies three or four times over several months before noticing an improvement, he says.
Part of therapy also includes increased salt intake combined with increased fluid intake, but diet changes alone may not be effective for treating patients with CFS or neurally mediated hypotension, warn researchers. "We believe salt plays an important role in blood pressure regulation, but it appears to be most effective when used in conjunction with drug therapies," says pediatric cardiologist Issam Bou-Holaigah, M.D., lead author of the study.
Neurocardiogenic syncope, neurally mediated syncope, vasodepressor syncope, vasovagal syncope and neurally mediated hypotension are different names for the same disorder. The condition commonly occurs when the autonomic nervous system, which controls heart rate and blood pressure response, misinterprets what the body needs during periods of upright posture and sends a message to the heart to slow down and lower blood pressure. This is the opposite of what the body needs at such times, says Jean Kan, M.D., Helen B. Taussig Professor and director of the division of pediatric cardiology. Neurally mediated hypotension occurs typically after exercise, long periods of standing or exposure to warm environments. If the heart slows down at these times -- when heart rate and blood pressure should be increasing -- lightheadedness, fainting and headaches are common results.
In contrast to all that is known about neurally mediated hypotension, CFS remains poorly understood. It is estimated that nearly 25 percent of the population will develop prolonged fatigue at some point in their lives. Chronic fatigue syndrome is a related but less common and more severe condition with worldwide prevalence of up to three per 1,000 people. It is defined as a profound fatigue lasting at least six months, often beginning abruptly after an apparent viral infection, and not explained by known medical or psychiatric disorders. The fatigue often worsens after physical exertion and other symptoms include lightheadedness and blurred concentration (see attached definition from the CDC). Many medical professionals used to dismiss CFS as primarily psychiatric, but these results suggest that NMH may be the physical underpinning for symptoms in a large portion of patients, says Calkins.
Bou-Holaigah was partially funded by the Saudi Arabian Oil Co. (Saudi ARAMCO).